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1.
J Pediatr Pharmacol Ther ; 24(4): 304-311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337993

RESUMO

OBJECTIVES: Assess the competency of community pharmacists in identifying errors in pediatric prescriptions and to determine how often pharmacists perform interventions known to mitigate the likelihood of error. The study sought to recognize factors that may impact the pharmacist's ability to identify and mediate these errors, and to detect barriers that limit the role of the pharmacist pediatric patient care. METHODS: A survey was distributed through the University of Illinois at Chicago College of Pharmacy Alumni Network and the Illinois Pharmacists Association email listservs. Pharmacists practicing in a retail setting within the last 5 years were included. Three prescription scenarios for commonly used pediatric medications with corresponding questions were created to assess a pharmacist's ability to identify errors. Demographics pertaining to the pharmacist and the practice site, as well as information about dispensing practices, were collected. Logistic regression was used to identify factors that might impact the pharmacists' ability to identify errors. RESULTS: One hundred sixty-one respondents began the survey and 138 met inclusion criteria. In 15% to 59% of scenario-based questions, pharmacists did not appropriately identify errors or interventions that would decrease the likelihood of error. Correct identification of doses was associated with total prescription volume in one scenario and with pediatric prescription volume in another scenario. Pharmacists did not consistently label prescriptions for oral liquids in milliliters or dispense oral syringes. Barriers to pharmacist involvement included availability and interest of the caregiver, ability to contact prescriber, and pharmacy staffing. CONCLUSION: Community pharmacists did not consistently identify medication errors or use interventions known to mitigate error risk.

2.
Proc Natl Acad Sci U S A ; 110(19): E1827-36, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23610440

RESUMO

The endosperm of cereal grains is one of the most valuable products of modern agriculture. Cereal endosperm development comprises different phases characterized by mitotic cell proliferation, endoreduplication, the accumulation of storage compounds, and programmed cell death. Although manipulation of these processes could maximize grain yield, how they are regulated and integrated is poorly understood. We show that the Retinoblastoma-related (RBR) pathway controls key aspects of endosperm development in maize. Down-regulation of RBR1 by RNAi resulted in up-regulation of RBR3-type genes, as well as the MINICHROMOSOME MAINTENANCE 2-7 gene family and PROLIFERATING CELL NUCLEAR ANTIGEN, which encode essential DNA replication factors. Both the mitotic and endoreduplication cell cycles were stimulated. Developing transgenic endosperm contained 42-58% more cells and ∼70% more DNA than wild type, whereas there was a reduction in cell and nuclear sizes. In addition, cell death was enhanced. The DNA content of mature endosperm increased 43% upon RBR1 down-regulation, whereas storage protein content and kernel weight were essentially not affected. Down-regulation of both RBR1 and CYCLIN DEPENDENT KINASE A (CDKA);1 indicated that CDKA;1 is epistatic to RBR1 and controls endoreduplication through an RBR1-dependent pathway. However, the repressive activity of RBR1 on downstream targets was independent from CDKA;1, suggesting diversification of RBR1 activities. Furthermore, RBR1 negatively regulated CDK activity, suggesting the presence of a feedback loop. These results indicate that the RBR1 pathway plays a major role in regulation of different processes during maize endosperm development and suggest the presence of tissue/organ-level regulation of endosperm/seed homeostasis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Endosperma/fisiologia , Proteína do Retinoblastoma/metabolismo , Zea mays/metabolismo , Ciclo Celular , Morte Celular , Proliferação de Células , Quinases Ciclina-Dependentes/metabolismo , Regulação da Expressão Gênica de Plantas , Genótipo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Interferência de RNA , Sementes/fisiologia , Zea mays/genética
3.
Proc Natl Acad Sci U S A ; 106(10): 4042-7, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19234120

RESUMO

Retinoblastoma-related (RBR) genes inhibit the cell cycle primarily by repressing adenovirus E2 promoter binding factor (E2F) transcription factors, which drive the expression of numerous genes required for DNA synthesis and cell cycle progression. The RBR-E2F pathway is conserved in plants, but cereals such as maize are characterized by having a complex RBR gene family with at least 2 functionally distinct members, RBR1 and RBR3. Although RBR1 has a clear cell cycle inhibitory function, it is not known whether RBR3 has a positive or negative role. By uncoupling RBR3 from the negative regulation of RBR1 in cultured maize embryos through a combination of approaches, we demonstrate that RBR3 has a positive and critical role in the expression of E2F targets required for the initiation of DNA synthesis, DNA replication, and the efficiency with which transformed plants can be obtained. Titration of endogenous RBR3 activity through expression of a dominant-negative allele with a compromised pocket domain suggests that these RBR3 functions require an activity distinct from its pocket domain. Our results indicate a cell cycle pathway in maize, in which 2 RBR genes have specific and opposing functions. Thus, the paradigm that RBR genes are negative cell cycle regulators cannot be considered universal.


Assuntos
Cromossomos de Plantas/genética , Replicação do DNA , Regulação da Expressão Gênica de Plantas , Genes do Retinoblastoma , Proteínas de Plantas/genética , Zea mays/citologia , Zea mays/genética , Regulação para Baixo/genética , Fase G2 , Genes de Plantas , Modelos Genéticos , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transformação Genética
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